CARCINOGENESIS

Vanja Cviji
Zagreb Medical School
2015/2016

Carcinogenesis is a multistep process at

both the phenotypic and the genetic level

It starts with a genetic damage:

Environmental
Chemical
Radiation
Viral
Inhereted

Four regulatory genes are the main

targets:
Growth

promoting proto-oncogenes

Proto-oncogene

mutation

oncogene
Growth
Genes
DNA

inhibiting (suppressor) genes

regulating apoptosis

repair genes

Main changes in the cell physiology that

lead to formation of the malignant
phenotype:
Self-sufficiency
Insensitivity
Evasion

to growth-inhibitory signals

of apoptosis

Limitless
Ability

in growth signals

replicative potential

to invade and metastsize

A) Self-sufficiency in growth
signals
Oncogenes derived by
mutations in protooncogenes
-GF,GRF, signal transducing
proteins, Nuclear
transcription factors ,
CDK )
promote cell growth in
the absence of
normal growthpromoting signals

B )Insensitivity to growthinhibitory signals

Tumor suppressor
genes control ( apply
brakes) cells
proliferation
If mutation caused
disruption to them
cell will become
insensitive to growth
inhibition
uncontrolled
proliferation
RB,Tp53,APC

C) Evasion of apoptosis
Apoptosis rapid and irreversible process
to efficiently eliminate dysfunctionalcells
genes

regulating apoptosis are factors in

malignant transformation

BCL-2

D)Limitless replicative potential

Normally progressive
shortening of telomeres
at the ends of
chromosomes

Telomerase active in
normal stem cells but
absent in somatic cells

In tumor cells :
activation of the
enzyme telomerase,
which can maintain
normal telomere length

F)Ability to invade and metastasize

-two step
event
1) Invasion
of
extracellula
r matrix
2)Vascular
disseminati
on and
homing of
tumor cells

Carcinogenic Agents

Chemicals

Radiation

Microbial agents

Chemicals:
Natural
Direct

or synthetic

reacting or indirect

Indirect

need metabolic conversion to be active

and carcinogenic

Indirect

chemicals are called procarcinogens and

their active end products are called ultimate
carcinogens

Direct ultimate chemical carcinogens as they have

electron-deficient atoms

Cigarette smoking ,animal fats during broiling meats

,smoked meats and fish

Radiation carcinogenesis
UV

rays of sunlight

X-rays
Nuclear

radiation

Therapeutic

radiations

Radiation has mutagenic effects:

chromosomes breakage, translocations, and
point mutations

Viral and Microbial oncogenesis :

Viral oncogenes carry genes that induce cell

replication as part of the viral life cycle

Viral infection mimics or blocks normal cellular

signals necessary for growth regulation

HPV, EBV,HBV

References

https://en.wikipedia.org/wiki/Telomere#Cancer

http://www.webmd.com/cancer/

https://en.wikipedia.org/wiki/Carcinogenesis